The extracellular matrix is an essential component of the tumor microenvironment and affects cancer progression. Weeraratna and colleagues have now uncovered that age-related reductions in the level of hyaluronan and proteoglycan link protein 1 (HAPLN1) stimulate neoangiogenesis and compromise the vascular integrity of intratumoral blood vessels. These biological modifications converge to fuel distant melanoma metastasis.

Your immune system should ideally recognize and attack infectious invaders and cancerous cells. But the system requires safety mechanisms, or brakes, to keep it from damaging healthy cells. To do this, T cells—the immune system’s most powerful attackers—rely on immune “checkpoints” to turn immune activation down when they receive the right signal. While these interactions have been well studied, a research team supported in part by NIH has made an unexpected discovery into how a key immune checkpoint works, with potentially important implications for therapies designed to boost or dampen immune activity to treat cancer and autoimmune diseases.¹

The checkpoint in question is a protein called programmed cell death-1 (PD-1). Here’s how it works: PD-1 is a receptor on the surface of T cells, where it latches onto certain proteins, known as PD-L1 and PD-L2, on the surface of other cells in the body. When this interaction occurs, a signal is sent to the T cells that stops them from attacking these other cells.

Cancer cells often take advantage of this braking system, producing copious amounts of PD-L1 on their surface, allowing them to hide from T cells. An effective class of immunotherapy drugs used to treat many cancers works by blocking the interaction between PD-1 and PD-L1, to effectively release the brakes on the immune system to allow the T cells to unleash an assault on cancer cells. Researchers have also developed potential treatments for autoimmune diseases that take the opposite tact: stimulating PD-1 interaction to keep T cells inactive. These PD-1 “agonists” have shown promise in clinical trials as treatments for certain autoimmune diseases.

Year 2021 😗😁😘

Researchers Prof. Judith Haendeler from the Medical Faculty and the molecular biologist Prof. Joachim Altschmied from the Department of Biology, together with their teams, have shown for the first time in the cardiovascular system that telomerase reverse transcriptase (TERT) within the mitochondria, the powerhouses of the cells, has a protective function in myocardial infarction. This work, which was performed together with other groups from the University Hospital Düsseldorf and the University Hospital Essen within the frame of the Collaborative Research Center 1,116, was recently published in the journal Circulation.

Cardiac muscle cells benefit from the increased mitochondrial function and are protected from cell death. Other cell types also profit from increased mitochondrial function such as fibroblasts, which are essential for stable scarring after an infarction, and endothelial cells, which are needed for vascularization and thus blood supply in the infarct area.

In the cell nucleus, TERT is a component of the so-called “immortality enzyme” telomerase, for the discovery of which the Nobel Prize in Physiology or Medicine was awarded in 2009. Meanwhile, it has been shown by the two research groups at HHU, that TERT is also present in mitochondria in the cells of the cardiovascular system. However, until now it has not been possible to clearly distinguish between its functions in these two cell organelles.